ACAT inhibition of alkamides identified in the fruits of Piper nigrum

Rho, Mun‐Chual; Lee, Seung Woong; Park, Hye Ran; Choi, Jung‐Ho; Kang, Ji Yun; Kim, Koanhoi; Lee, Hyun Sun; Kim, Young Kook

doi:10.1016/j.phytochem.2006.11.025

Cited by 35 publications

(20 citation statements)

References 20 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Effect of EA on ACAT activity was tested by the isotope labeling method as reported previously [20]. In brief, the prepared microsomes were unfrozen and dissolved at 37°C water bath.…”

Section: Methodsmentioning

confidence: 99%

Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

Han

Peng

2014

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA) and oleanolic acid (OA) at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0) to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, acyl-CoA:cholesterol acyltransferase (ACAT), and diacylglycerol acyltransferase (DGAT) in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

show abstract

“…Effect of EA on ACAT activity was tested by the isotope labeling method as reported previously [20]. In brief, the prepared microsomes were unfrozen and dissolved at 37°C water bath.…”

Section: Methodsmentioning

confidence: 99%

Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

Han

Peng

2014

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Ribeiro et al (2004) reported that the alkaloid piperine showed activity against Trypanosoma cruzi with IC 50 at 7.36 M. Various species from this genus have been used in South East Asia and South Asia for a variety of ethnopharmacological purposes (Wuttidhammaved, 1997). This genus of plants is well known for the presence of several chemical components including N-isobutyl amide of octadecatrans-2-cis-4-dienoic acid (Siddiqui et al, 1997), isopiperolein B (Srinivas and Rao, 1999), piperine, piperchabamide D, dehydropipermolanine and dehydropopermoline (Dagli, 2004;Rho et al, 2007). Moreover, pipernonaline, guineensine, isobutylamide of 11-(3,4-methylenedioxy-phenyl)undeca-2,4,10-trienoic acid, piperchabamides A, piperchabamides B, piperchabamides C, piperlonguminine, retrofractamide B, N-isobutyl-(2E,4E,14Z)-eicosatrienamide and methylpiperate were isolated from Piper chaba by Dagli (2004).…”

Section: Plants With Anthelmintic Activitymentioning

confidence: 99%

“…Moreover, pipernonaline, guineensine, isobutylamide of 11-(3,4-methylenedioxy-phenyl)undeca-2,4,10-trienoic acid, piperchabamides A, piperchabamides B, piperchabamides C, piperlonguminine, retrofractamide B, N-isobutyl-(2E,4E,14Z)-eicosatrienamide and methylpiperate were isolated from Piper chaba by Dagli (2004). Several compounds, including pipercyclobutanamides A, B (Fujiwara et al, 2001), dipiperamides A, B, C (Tsukamoto et al, 2002), germacrene D, limonene,ˇ-caryophyllene, -phellandrene,ˇ-pinene,˛-pinene, cis-ˇ-ocimene (Jirovetz et al, 2002), piperylin, alkamide, retrofractamide A, pipercide, pellitorin, and dehydroretrofractamide C were discovered in Piper nigrum (Rho et al, 2007).…”

Section: Plants With Anthelmintic Activitymentioning

confidence: 99%

In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand

Atjanasuppat

Wongkham

Meepowpan

et al. 2009

Journal of Ethnopharmacology

111

View full text Add to dashboard Cite

“…Candidate selection was primarily based on structural similarities to the control and Dock Score which considers the internal energies of ligands and their corresponding protein-ligand interaction energy. Guineensine37 and Retrofractamide A38, compounds originating from Piper longum 3940 have Dock Scores of 61.45 and 54.01, respectively, and were selected as candidates (Table 2). Front and side views of the docking poses of the TCM candidates and the control at the modeled anandamide binding site are illustrated in Figure 2b and 2c.…”

Section: Resultsmentioning

confidence: 99%

Drug Design for Neuropathic Pain Regulation from Traditional Chinese Medicine

Tou

Chang

Lee

et al. 2013

Sci Rep

View full text Add to dashboard Cite

FAAH-like anandamide transporter (FLAT) regulates anandamide transport for hydrolysis and may be an attractive drug target for pain regulation. We aimed to discover potential FLAT antagonists from traditional Chinese medicine (TCM) using virtual screening, ligand-based drug design and molecular dynamics simulation (MD). Guineensine and Retrofractamide A exhibited high Dock Scores in FLAT. Consensus from multiple linear regression (MLR; R2 = 08973) and support vector machine (SVM; R2 = 0.7988) showed similar bioactivities for Guineensine and the FAAH-1 inhibitor (9Z)-1-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)octadec-9-en-1-one. Contour of Guineensine to CoMFA and CoMSIA features also imply bioactivity. MD revealed shake or vibration in the secondary structure of FLAT complexed with Guineensine and (9Z)-1-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)octadec-9-en-1-one. Ligand movement might contribute to protein changes leading to vibration patterns. Violent vibrations leading to an overall decrease in FLAT function could be the underlying mechanism for Guineensine. Here we suggest Guineensine as a drug-like compound with potential application in relieving neuropathic pain by inhibiting FLAT.

show abstract

ACAT inhibition of alkamides identified in the fruits of Piper nigrum

Cited by 35 publications

References 20 publications

Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand

Drug Design for Neuropathic Pain Regulation from Traditional Chinese Medicine

Contact Info

Product

Resources

About